THE OI REPORT: A Critical Review of the Treatment & Prophylaxis of AIDS-Related Opportunistic Infections (OIs)

OTHER BACTERIAL INFECTIONS
by Evan Wilder and Theo Smart

INTRODUCTION
"Bacteria, by any reasonable criterion, were in the beginning, are now, and ever shall be the most successful organisms on earth" (Gould 1996). Bacteria are single-celled organisms found everywhere in nature, often living in symbiosis with other life forms. The human body plays host to trillions of bacteria, most of which are beneficial. For example, much of a person's diet would be indigestible without the aid of bacteria in the gut. However, other bacteria are a significant cause of disease, particularly in people with HIV, who are at increased risk for bacterial infections due to HIV-associated immunologic defects. Most bacterial infections in people with HIV are caused by organisms such as Streptococcus pneumoniae, Haemophilus influenzae, Staphylococcus aureus, Salmonella species, and increasingly Pseudomonas aeruginosa. Rhodococcus equi, Listeria monocytogenes, Shigella species, Campylobacter and Nocardia asteroides. are less common but still observed. Most of these infections can be organized by their clinical syndromes which include pneumonia, sinusitis, gastrointestinal disease, and skin or soft tissue infections. People with HIV and bacterial infections are more susceptible to bacteremia and sepsis, occasionally complicated by endocarditis, a bacterial infection of the linings of the heart.

PATHOGENESIS
Although most opportunistic processes in HIV disease occur when CD4 cell counts are quite depressed, bacterial infections with organisms such as S. pneumoniae, H. influenzae, and Salmonella species can occur at any CD4 lymphocyte count (Witt 1987; Polsky 1986). In a normal host, the immune response to these bacteria is a two-step process. Invading organisms are phagocytized and epitopes presented to T-helper cells, alerting the immune system to the presence of the infection. Subsequently, the host produces specific antibodies that enhance phagocytosis by the neutrophils and the reticuloendothelial system. People with HIV are particularly prey to persistent infection because of numerous abnormalities in these processes. These include immunologic defects in T cells, B cells, macrophages, (McGrath 1994) and polymorphonuclear cells such as neutrophils (Ellis 1988).

Changes in the humoral immune system are among the first immunologic effects of HIV infection (Terpstra 1989). In the normal host, local mucosal (IgA) antibodies prevent bacterial adherence to and colonization of mucosal surfaces (Janoff 1992). In HIV-infected subjects, there are decreased numbers of antibody-producing cells and antibodies at mucosal sites (Muller 1989), which may contribute to an increased susceptibility to bacterial infections. HIV infection also alters systemic defenses to these infections. HIV-infected patients may lose their ability to produce specific antibody responses to acute infections or vaccines (Polsky 1986), while simultaneously undergoing nonspecific B cell hyperactivation (Lane 1983). IgG2 antibodies, which may play a role in the control of pneumococcal disease (Janoff 1992) also appear to be decreased among HIV-infected individuals.

There are numerous reports of impaired neutrophil function (reduced chemotaxis, phagocytosis, and bacterial killing) in patients with HIV infection (Ellis 1988). A recent study by Kaykova and colleagues compared neutrophil function in HIV-infected and uninfected individuals, measuring oxidative burst by neutrophils exposed to E. coli, S. aureus and C. albicans. They found that neutrophils from the positive individuals produced more oxygen radicals after stimulation with bacteria, but fewer neutrophils participated in phagocytosis (Kaykova 1997). In addition, neutropenia is becoming more common because of the use of myelotoxic drugs such as AZT, ganciclovir and other bone marrow suppressive agents. Finally. clearance of bacteria by tissue macrophages in the liver and spleen is delayed and decreased in HIV-infected patients (McGrath 1994; Bender 1985, 1987).

EPIDEMIOLOGY
Currier and Feinberg detailed how frequent some bacterial syndromes are in patients with advanced HIV disease (Currier 1996). They looked at the rate of bacterial infections among 398 patients in two ACTG studies. Participants had a median CD4 cell count of 35 cells; 79% were receiving antiretroviral therapy; PCP prophylaxis was used by 99% (trimethoprim-sulfamethoxazole -- henceforth TMP/SMX and also known as Bactrim or Septra - in 75%) and MAC prophylaxis by 89% (rifabutin in 32%, clarithromycin by 32%, rifabutin and clarithromycin in 23% and azithromycin in 3%). During a median follow-up of 639 days, 168 patients (42%) experienced 241 bacterial infections. The most common bacterial infections were sinusitis (8.5 per 100 patient years, py), bacterial pneumonia (5.0 per 100 py), bronchitis (4.1 per 100 py), and skin and soft tissue infections (3.5 per 100 py).

Bacterial infections appear to vary by population and disease stage. Greenberg and colleagues compared rates of bacterial infections in different populations by reviewing nearly 3,000 outpatient records through 1989. Injecting drug users (IDUs) were more likely to have bacterial pneumonia than gay men. Non-Haitian blacks were more likely to have Salmonella sepsis than whites. There were no differences in gender. Overall, 16% of the records reported cases of bacterial pneumonia.

Selwyn and colleagues reported that in a large cohort of HIV-infected injection drug users, bacterial infections were both a significant predictor of progression to AIDS and a substantial cause of pre-AIDS morbidity and mortality. This prospective study of patients from a methadone clinic was conducted in New York City from July 1985 through December 1990. Over three years of follow-up, 55 (17%) received an AIDS diagnosis. Major outcomes before the development of AIDS included pyogenic (pus-producing) bacterial infections, pneumonia and sepsis. The rate of pneumonia and sepsis was 8.0 episodes per 100 patient years of follow-up. Bacterial infections were most common in HIV-infected patients with CD4 counts below 200. The most striking finding was that 13 of 318 asymptomatic HIV-positive patients (died of bacterial infections, as compared with only 1 of 411 HIV-negative patients examined (4% vs. 0.2%) (Selwyn 1992).

In a similar study conducted in Amsterdam, this difference in mortality was not observed among those without AIDS (Mientjes 1992) - though this may be more of a reflection on differences in health care available to IDUs in the two cities rather than on the intrinsic morbidity of the condition. However, in Amsterdam, bacterial pneumonia was four times more common among HIV-positive IDUs than among HIV-negative ones; the rate appeared to increase over time.

One small study by Keiser and colleagues suggested that neutropenic patients with AIDS are at increased risk of bacterial infections compared to non-neutropenic AIDS patients. Bacteremia was significantly more likely to develop among the study's 29 neutropenic patients with AIDS than in matched non-neutropenic patients with comparable CD4 cell counts, antiretroviral usage and presence of indwelling catheters (Keiser 1994). HIV-negative patients with neutropenia are also at increased risk of developing bacterial infections.

Omenaca and colleagues from St. Vincent's in New York City reported a retrospective survey of 88 episodes of bacteremia in 80 HIV-infected patients identified over five months and followed for 30 days. 64.8% of the infections were Gram-positive. 44.8% of them derived from intravascular catheter infections, and 17% were pneumonias. The overall mortality rate was 28.8%. By multiple regression analysis, predictors of mortality were as follows:

CLINICAL SYNDROMES

BACTERIAL PNEUMONIA
Bacterial pneumonia is now the most common cause of pneumonia requiring hospitalization in HIV-infected patients in some institutions (Ruizi 1992; Magnenat 1991). Bacterial pneumonias account for up to 40-50% of hospital admissions for lower respiratory tract infections among people with HIV (Arzuaga 1994). S. pneumoniae and H. influenzae cause the majority of pyogenic pneumonias in HIV-infected persons. (Witt 1987; Polsky 1986). A number of other organisms may also cause pneumonia, such as Pseudomonas aeruginosa, Rhodococcus equi, Nocardia species and Bordetella bronchiseptica.

Bacterial pneumonia can occur at any time during the course of HIV infection and is often the first manifestation of HIV disease. Witt and colleagues reported bacterial pneumonia in 16 of 28 (57%) patients with advanced disease and 14 of 31 (45%) patients with symptomatic middle-stage HIV disease over a 44-month period (Witt 1987). A Spanish survey found that pneumococcal pneumonia was the first clinical manifestation of HIV infection in 48% of patients with HIV disease (Garcia-Leoni 1992). In this study, 72% of all patients under 40 years old diagnosed with pneumococcal pneumonia were co-infected with HIV.

There is a very high rate of pneumococcal bacteremia in people with HIV (Selwyn 1992; Janoff 1992). In one report, from 1983 to 1987 in San Francisco, the estimated annual rate of pneumococcal bacteremia was 9.4 cases per 1,000 patients with advanced HIV disease, while the rate of bacteremia in all community patients from 20 to 55 years old is 0.07 cases per 1,000 per year -- greater than a 100-fold increase in risk (Brieman 1990).

Rosenberg and colleagues reported that bacterial pneumonias are becoming more common in AIDS. Of 101 AIDS patients admitted to a single hospital intensive care units due to infection, 30 (30%) had bacterial or fungal pneumonia. The non-PCP pneumonias were most commonly caused by Pseudomonas aeruginosa (six, 21%), Pneumococcus, S. aureus, Klebsiella (three each, 10%) or were fungal (four, 13%) (Rosenberg 1997).

This is not the only study to note a high rate of Pseudomonas. Numerous other reports suggest that the incidence of this bacterial infection may be increasing over time in people with AIDS (Baron 1993; Kielhofner 1992; Franzetti 1992). Risk factors for Pseudomonas infection include prior AIDS diagnosis and more hospitalizations (Fichtenbaum 1994), suggesting that it may be more common in very advanced HIV disease, and that its increasing incidence may be related to the increased survival of people with severe immunosuppression. Here the mean CD4 count of patients with Pseudomonas infections was 11 cells and the mortality rate was 36%.

Chaisson and colleagues assessed risk factors and trends in bacterial pneumonia among 2,888 patients prospectively followed over 4,029 person years from 1989-1996. Annual incidence ranged from 7.5-11.5 cases per 100 patient years, with no decrease during 1996 - the year which witnessed the introduction of protease inhibitors and, with it, dramatic reductions in many other OIs. Drug users were more likely to develop bacterial pneumonia than non drug users (14% vs. 11%), as were blacks compared with non-blacks (14% vs. 9%). Lower CD4 counts at baseline and during follow-up increased the risk of bacterial pneumonia. TMP/SMX did not appear to protect against this infection. While a history of Pneumocystis increased the relative risk (RR=2.6), TMP/SMX did not appear protective against bacterial pneumonia, suggesting increased bacterial resistance. By contrast, the use of macrolide prophylaxis against MAC (azithromycin or clarithromycin) reduced the risk (RR=0.27), though this did not reach statistical significance. In summary, bacterial pneumonia remains common and its incidence did not decrease in the first year of widespread protease use (Chaisson 1997).

Clinical Presentation
The clinical presentation and duration of bacterial pneumonia in people with HIV infection does not differ dramatically from that in the normal patient, with the acute onset of fever, shortness of breath, productive cough, chest pain, and purulent sputum (Schlamm 1989; Chaisson 1988). Laboratory abnormalities are similar regardless of serostatus with elevated white blood cells, hypoxia and hypocarbia (oxygen and carbon dioxide deficiencies in the blood) that correlate with the severity of the pneumonia and underlying lung disease (Gerberding 1986). Chest radiographs show unilobar or multilobar air space consolidation. Cavitation and pleural effusions are relatively uncommon in HIV-infected patients.

Usually the presentation differs significantly from that of PCP. Chest radiographs may help to distinguish bacterial pneumonia from other causes of lung disease. However, there are exceptions. For example, bacterial pneumonia caused by Hemophilus influenzae may have a more gradual onset, without fever, a non-productive cough, multi-lobar disease and severe inflammation -- symptoms that resemble those of PCP. Likewise, in a Swiss report, 47% of HIV-infected patients with pneumonitis had radiographic presentations indistinguishable from the typical appearance of PCP (Pesola 1992). This is not typical, as an unusually high number of patients with pneumococcal pneumonia in this study presented with interstitial infiltrates.

Some less common pathogens may also cause bacterial pneumonia, and should be considered when making a diagnosis. Rhodococcus equi causes cavitary lung disease (deterioration of lung tissue causing holes) viewable on chest X-rays. In addition to respiratory symptoms and fever, this infection may cause extrapulmonary disease including gastrointestinal infections and brain abscesses (Verville 1994). Nocardia is less frequent and tends to occur in more advanced patients (Martos 1993). Its appearance on chest-X-ray is variable, but this infection should be suspected in any patient with a subacute onset of disease, particularly if a cavitary or mass lesion is observed. This infection may also disseminate to the central nervous system (CNS) and skin (Uttamchandani 1994). Bortetella bronchiseptica should be considered when pneumonia symptoms include interstitial infiltrates, severe disabling whooping-like cough, and the absence of fever (Sullivan 1994). It may be associated with sinusitis.

Diagnosis
In order to distinguish between pathogenic organisms with similar symptoms, the initial evaluation should include blood cultures and sputum examination by Gram's Stain. A Danish physician named C.J. Gram developed a method to differentiate bacteria under the microscope after the application of a stain. Staphylococci, the cause of many abscesses, and Streptococci turn purple in this stain, whereas bacteria such as Salmonella turn red. Gram's stain may suggest the diagnosis if there are few epithelial cells, many polymorphonuclear cells (PMNs), and a predominant bacterial morphology. Sputum cultures are less helpful since the organism can be part of the normal oropharyngeal flora. The Gram's stain does not detect PCP. Blood cultures are very specific and should be obtained for all HIV-infected patients with suspected bacterial pneumonia. The incidence of pneumococcal bacteremia in patients with HIV infection and pneumonia has ranged from 25% to over 75% (Witt 1987; Polsky 1986). H. influenzae bacteremia is much less frequent; only 9% of patients with Haemophilus pneumonia had positive blood cultures in one report (Schlamm 1989).

Treatment
If the clinician has correctly identified the infectious agent, and treatment has been tailored to that specific organism, HIV-positive patients with bacterial pneumonia usually respond rapidly to antibiotic treatment, despite their depressed immune systems and high levels of bacteremia. Gerberding reported that 90% of patients with HIV infection and pneumococcal pneumonia clinically improved within three days of appropriate antimicrobial therapy treatment; by day five, 80% no longer had fevers (Gerberding 1986). There appears to be no need to extend the duration of treatment (Magnenat 1991).

For patients with pneumococcal infections, penicillin, erythromycin or other macrolides are appropriate. H. influenzae should be treated for approximately ten days with a second generation cephalosporin. If the organism is beta-lactamase negative, the patient can be switched to ampicillin or amoxacillin. For beta-lactamase producing H. influenzae, amoxacillin-clavulanic acid, an oral cephalosporin, azithromycin or clarithromycin can be used.

Patients who do not respond to treatment may have a concurrent opportunistic infection such as PCP. In a review of hospitalized HIV-infected patients with pneumonia due to encapsulated bacteria at San Francisco General Hospital, eight patients failed to improve by day five (Gerberding 1986). Five had concurrent PCP. Others have reported similar cases (Schlamm 1989).

For patients with particularly severe or atypical presentations or a non-diagnostic Gram's stain, empiric therapy should be considered with antimicrobial agents active against PCP as well as S. Pneumonia and Hemophilus influenzae while results from diagnostics test for PCP are pending. TMP/SMX is effective against all three pathogens. If pentamidine or atovaquone is used for PCP, then ampicillin or cefuroxime should be added.

The more unusual pathogens such as Rhodococcus equi, Nocardia species, and Bordetella bronchiseptica are more a challenge to treat, and therapy may need to continue for a longer duration. Rhodococcus equi has been successfully treated with prolonged erythromycin and rifampin. Chronic treatment with at least two antibiotics may be necessary as relapse is common. Rhodococcus equi is usually sensitive to vancomycin, chloramphenicol, aminoglycosides, tetracycline, doxycycline, and flouroquinolones. Sulfonamides are considered the primary therapy for Nocardia, but due to allergic reactions broad spectrum cephalosporins, amikacin, minocycline, rifampin, or imipenem are often used. Relapses may occur in HIV-infected patients treated for only a short duration, and lifelong suppressive therapy may be required. Finally, there has been one report of successful treatment of Bordetella bronchiseptica with prolonged therapy with imipenem/cilastin followed by amoxicillin/clavulante (Sullivan 1994). Despite the good response to therapy for most cases of bacterial pneumonia, recurrence is common in people with HIV. Several reports described recurrent pneumococcal infection in 8 to 25% of HIV-infected patients as compared with seven percent of controls (Polsky 1986; Gerberding 1986).

Prevention
Given the high rate of bacterial pneumonia, frequent recurrence and dangerous bacteremia in people with HIV, prevention is extremely important. Unfortunately, several groups have reported that antibody responses to vaccination are decreased in people with HIV, and the more severe the underlying immunosuppression, the lower the antibody titers (Huang 1987; Ballet 1987; Klein 1989). Polsky and colleagues found that 25% of their patients with bacterial pneumonia had recurrences within six months (Polsky 1986). Three patients tested for type-specific pneumococcal capsular polysaccharide antibody had failed to develop protective antibody levels following pneumococcal infections, while others failed to respond to the pneumococcal vaccine. Nevertheless, many patients are able to mount a protective antibody response (Glaser 1991; Janoff 1992; Huang 1987).

The U.S. Public Health Service and the Infectious Disease Society of America published guidelines for the prevention of respiratory bacterial infections (CDC 1997). To prevent pneumococcal infections, the guidelines state that adults should receive a single dose of the pneumococcal vaccine (along with annual influenza vaccination) as soon as possible after HIV infection has been diagnosed. H. influenzae type B vaccination should also be considered, but the response may depend both upon the influenza vaccine being used and the patient's stage of HIV disease. Steinhoff and colleagues reported that in asymptomatic and early symptomatic HIV-positive men, the antibody responses to one (the polysaccharide-mutant diphtheria-toxoid conjugate vaccine) were three-fold greater than to the polysaccharide (PRP) vaccine. However, in men with AIDS, the PRP vaccine induced a greater response. Another concern about this vaccine is that most H. influenzae infections are not due to type B organisms.; in one study, only 33% of isolates were type B (Steinhart 1991). Thus the vaccine's protective abilities remain far from certain.

Passive immunotherapy with immunoglobulin G (IVIG) decreases the rate of bacterial infections in HIV-infected children with CD4 cell counts above 200 (see below). It is unknown whether same is true in adults. Different studies using different IVIG doses have generated different results. One study demonstrated decreased mortality among HIV-infected patients treated with IVIG, but no significant reduction in the rate of bacterial infections (Brunkhorst 1990). In another small study, there was a decrease in recurrent bacterial infections, but a higher rate of OIs among IVIG recipients (Mars 1994). Clearly, randomized studies of those adults at highest risk for developing bacterial infections are needed before this expensive therapy can be recommended.

Finally, clinicians should consider antibiotic prophylaxis for individuals with recurrent invasive bacterial infections. A number of studies of TMP/SMX for PCP prophylaxis have noted a reduction in the incidence of bacterial infections (Hardy 1992; Currier 1997; Direnzo 1997). In ACTG 815, prophylaxis with clarithromycin (relative risk 0.73) or TMP/SMX (RR 0.74) and receipt of H. flu vaccine (RR 0.7) appeared to protect against the development of bacterial infections (Currier 1997). An Abbott-sponsored study also found that clarithromycin prophylaxis for MAC reduced the development of community acquired pneumonia. In this study of 678 AIDS patients randomized to clarithromycin 500 mg twice daily or placebo, 68 episodes of pneumonia were reported over a median treatment period of 10.9 months. Forty four (64%) of the episodes occurred on placebo (p=0.010). No pneumonia due to a clarithromycin-resistant organism was seen. Nevertheless, there are concerns that the chronic administration of antibiotics may lead to the development of resistance. In one study, 57% of pneumococcal isolates from HIV-infected patients were found to have reduced susceptibility to TMP/SMX (de la Rubia 1994).

ACTG 981, a substudy of ACTG 081, assessed the incidence of bacterial infections among 842 HIV-infected individuals with fewer than 200 CD4 cells who were receiving AZT along with either aerosolized pentamidine (AP), dapsone, or TMP/SMX for primary prophylaxis of Pneumocystis carinii pneumonia (PCP). The intent-to-treat analysis indicated that TMP/SMX significantly reduced the risk of any bacterial infection (p=0.02) and infectious diarrhea (p=0.04) compared to AP; and any bacterial infection (p=0.01) and sinusitis/otitis media (p=0.04) compared to dapsone. Interestingly, AP reduced the risk of sinusitis/otitis media (p=0.03) compared to dapsone. Overall bacterial infection rates per 100 person-years of follow-up were 31, 39 and 38 for TMP/SMX, dapsone and AP. Median survival was 39 months in all three groups. The investigators concluded that initiating prophylaxis with TMP/SMX was the superior strategy for preventing bacterial infection - as it was for preventing Pneumocystis - with most of the advantage manifest in preventing bacterial diarrhea, sinusitis, and otitis media (Dirienzo 1997).

SINUSITIS
Sinusitis, or inflammation of the sinuses, is common among HIV-infected patients (Godofsky 1992; Zurlo 1992). It may be acute, recurrent or chronic. One report suggests that sinusitis occurs in as many as 30% of HIV-positive adults (Small 1993). Sinusitis may be caused by a number of factors: allergies, viruses or opportunistic bacteria, sometimes working in concert. Secondary bacterial infections of the paranasal sinuses are frequent. Predisposing factors include anything that blocks drainage of the sinuses -- nasal polyps, a deviated septum, or adenoids.

The same organisms which cause acute sinusitis in the immunocompetent patient are found in those with HIV, namely Streptococcus pneumoniae, Moraxella catarrhalis, and H. influenzae. Thompson and colleagues report that many HIV-infected patients with sinusitis are infected with Staphylococcus epidermidis (Thompson 1993). S. aureus has been found in acute sinusitis, but is more common in chronic disease, often in association with anaerobic bacteria (Sooy 1987). Increasingly, Pseudomonas aeruginosa is the cause of chronic sinusitis in AIDS patients with advanced disease (von Schoennberg 1993). Godofsky and colleagues report that it accounts for up to 15% of cases of chronic sinusitis in the HIV-infected population (Godofsky 1992).

Clinical Manifestations
Sinusitis should be considered in differential diagnosis of any HIV positive individual with fever, headache, nasal congestion and drainage. Often, these symptoms are initially associated with pulmonary infections. Sometimes they may be due to primary infection by a rhinovirus or other pathogen. However, duration of symptoms without improvement for more than ten days suggests secondary bacterial infection (Zurlo 1992; Godofsky 1992). One recent study of S. aureus nasal colonization in HIV-positive and negative drug users found a higher rate of colonization among users of inhaled drugs (odds ratio 2.36, 95% C.I. 1.10-5.10) and women (OR 1.97, C.I. 1.09-3.57). Overall, HIV-infected drug users did not have increased rates of nasal colonization relative to their HIV-negative counterparts (Holbrook 1997).

The signs and symptoms of acute and chronic sinusitis differ slightly. Acute sinusitis includes nasal congestion, purulent nasal discharge, fever, and facial pain that increases with movement. Chronic sinusitis symptoms are fewer, and milder but last much longer (for more than a month, often despite antibiotic treatment). Symptoms include nasal congestion and discharge, intermittent pain that is vague rather than sharp; and post-nasal drip that causes a chronic nonproductive cough. Fever is rare.

Diagnosis
For mild presentations of acute sinusitis, clinicians often make the diagnosis based on clinical grounds and treat empirically with antibiotics and decongestants. Cases that do not respond to empiric therapy are particularly severe or appear to be inducing fever call for a more aggressive approach to diagnosis. This may require imaging studies and attempts to culture the organism. Tests should be performed for granulomatous disease, ciliary dysfunction, and hypogammaglobulinemia (Tami 1992). Clinicians must keep in mind that the condition may not be caused by bacteria, but by an opportunistic process. X-ray studies may reveal extensive paranasal sinus disease, but CT scanning more clearly defines the extent of the infection and helps detect bone and fungal involvement or tumors (Zurlo 1992). While it may be necessary to conduct a sinus tap (puncture) to obtain organisms for culturing, cultures derived from the drainage from accessible sinuses may provide good bacteriologic information. Should that fail, a nasal endoscopy (insertion of a device which examines the nasal canal) can be valuable for diagnosing sinusitis and for the evaluation of therapeutic response.

Therapy
No comparative studies have been conducted in people with HIV and sinusitis, but most reviews note that standard outpatient therapy with antibiotics and nasal decongestants are usually effective in this population. Tami and colleagues suggest that while amoxicillin (500 mg three times a day) or TMP/SMX twice daily are acceptable for primary treatment, amoxicillin with clavulanate (Augmentin) (500 mg three times a day) or an oral cephalosporin, such as cefuroxime axetil (Ceftin) (250 mg twice daily) or cefixime (Suprax), may be more effective. Treatment should last for at least three weeks (Tami 1992).

Decongestant therapy with agents such as pseudoephedrine, 120 mg every 12 hours for three weeks, is also recommended. Wawrose and colleagues report that guaifenesin (Humibid L.A., 1,200 mg every 12 hours) may thin nasal secretions and decrease nasal congestion (Wawrose 1992).

Chronic sinusitis or infections resistant to standard therapy become much more common as CD4 counts decrease and immune function diminishes. In such cases, therapy should be continued for five to six weeks, and the choice of antibiotic therapy should be culture-directed. Otherwise, antibiotics should be used which cover all bacteriologic bases, including S. aureus, anaerobic bacteria, and P. aeruginosa (Tami 1992). Amoxicillin with clavulanate (500 mg three times a day) provides poor coverage for P. aeruginosa but the addition of metronidazole (Flagyl, 250 mg two times a day) or clindamycin (Cleocin, 300 mg three times a day) improves the clinical response. Tami and colleagues also recommend ciprofloxacin (Cipro, 500 mg two times a day) plus clindamycin (300 mg three times a day), especially for P. aeruginosa (Tami 1992).

In addition to decongestant treatment, topical nasal steroids (such as Rhinocort) are routinely used and continued indefinitely for chronic sinusitis to decrease inflammation and reduce mucosal swelling to allow proper drainage of the nasal passages (Tami 1992).

When all other medical options have been exhausted, surgery is sometimes performed to enhance drainage and obtain cultures and biopsy specimens to rule out unusual opportunistic pathogens. Sooy reports that endoscopic sinus surgery may result in symptomatic improvement. However the benefits may be transient, and it is not clear that these benefits justify the procedure in severely immunocompromised patients.

GASTROINTESTINAL INFECTIONS
Enteric bacterial infections that cause diarrhea and malabsorption, as well as bacteremia, are both more frequent and more virulent in HIV-infected individuals (Smith 1988; Kotler 1995). Bacteria may cause inflammation and destruction in the small intestine or the colon, interfering with nutrient and fluid absorption. Some pathogens cause this inflammation by directly attaching or adhering to the cells lining the intestinal tract, others by the production of enterotoxins.

Common enteric bacterial pathogens in people with HIV include Salmonella and Shigella species, Listeria, Vibrio species and Campylobacter jejuni (Angulo 1995). With the exception of Shigella, these are primarily food-borne pathogens; people with HIV should be cautious when eating raw or undercooked seafood -- especially shellfish -- poultry, meat, or dairy products -- especially if unpasteurized. Finally, one of the natural intestinal flora, Clostridium difficile, is more prone to overgrowth in people with HIV due to their increased use of antibiotics.

Epidemiology
Historically, the most commonly isolated bacterial pathogen in people with AIDS was Salmonella (Sperber 1987). There are no data available on its incidence in people with HIV (Angulo 1995). In one epidemiologic study in San Francisco conducted from 1982-1986, the incidence of salmonellosis in people with AIDS was almost 400 cases per 100,000 persons per year, a rate twenty times as great as reported for people without AIDS (Celum1987). Forty-five percent of the people with AIDS and salmonellosis in this study were bacteremic, as opposed to 9% of those with salmonella in the uninfected. Forty-five percent of patients who did not receive maintenance antibiotics had a recurrence of septicemia. Recurrent Salmonella bacteremia in an HIV-positive person is an AIDS-defining condition. An Italian study between 1987-1989 found an even higher incidence of Salmonella in people with AIDS: 2,000 cases per 100,000 people per year - 100 times the incidence in the uninfected (Tocali 1991).

However, most of these studies were conducted in the 1980s before the widespread use of antiretrovirals or PCP prophylaxis with TMP/SMX which is active against Salmonella species. The current incidence of Salmonella appears to be greatly decreased.

Campylobacter jejuni also appears much more common in people with AIDS. Sorvillo and colleagues reported that between 1983 and 1987 in Los Angeles County, there was an average of 519 cases per 100,000 people per year among people with AIDS -- 39 times higher than in the uninfected (Sorvillo 1992). The incidence in less immune compromised people with HIV is unknown. Infections have been reported to occur in people with higher CD4 cell counts, but the median CD4 cell count in 30 patients with campylobacteriosis treated at one hospital was 108 (Nelson 1992). Other Campylobacter species are being observed with increased frequency.

The incidence of Listeria among the general population is 0.7 cases per 100,000 people per year, but among HIV-infected individuals, the incidence is as high as 52 cases per 100,000 people per year (Jurado 1993). Among people with AIDS, it is even higher -- roughly 145 times the incidence reported for the general populace. Early reports from San Francisco and Los Angeles suggested even higher rates, suggesting that the use of TMP/SMX and other antibiotics may have reduced its frequency (Angulo 1995).

Vibrio are salt-living, free-loving bacteria that live symbiotically with shellfish in the Gulf of Mexico. Although the incidence of Vibrio infections in people with HIV may not be great, the infections are particularly severe, leading to septicemia that is frequently life-threatening, particularly in people with pre-existing liver disease (Whitman 1993; Klontz 1988). The FDA has warned against eating Gulf Coast oysters -- particularly by the immunosuppressed -- due to the danger of Vibrio infection.

Although it is probably under-reported to the CDC, the incidence of Shigellosis is believed to be around 7.5 cases per 100,000 people per year (Blaser 1989). It is unclear whether the incidence is higher in people with HIV, although Shigella flexneri, a species that is sexually transmitted among gay men, may be seen with increased frequency in the earlier stages of HIV disease, perhaps in association with HIV transmission (Nelson 1992). As with Vibrio, the infections may result in much more serious disease in people with HIV, often leading to recurrent septicemia (Huebner 1993).

Kotler and colleagues carried out a retrospective review of all intestinal biopsies carried out among HIV-infected patients at a New York clinic during 1991 "to determine the prevalence of adherent bacteria in histologic specimens examined by light microscopy." Sixty-six HIV-infected individuals were evaluated that year for diarrhea, weight loss and other GI symptoms. Forty-two individuals had CDC-defined AIDS, and 24 did not. Adherent bacteria were found in 17% of all patients with AIDS; the infection was centered in the cecum and right colon. These infections were associated with weight loss (p<0.005) and CD4 counts below 100. "Eight of nine patients treated with antibiotics had symptomatic improvement. Bacterial cultures of rectal biopsies... yielded Eschericia coli in 12 of 18 cases; aggregative adherence was seen in six." (Kotler 1995).

Clinical Manifestations and Diagnosis
Patients with these enteric infections typically have high fever, abdominal pain, and diarrhea, which may be bloody (particularly with Shigella). Nevertheless, since so many things (including diet or medication) can cause diarrhea in a person with HIV, clinicians should remain suspicious for every imaginable offender (Dieterich 1994). The type of diarrhea may suggest the location of the infection, for example, infrequent large volume diarrhea suggest the small bowel, while frequent, small volume, but bloody diarrhea indicates colitis. (Salmonella and unusual Campylobacter species tend to infect the small bowel, while Shigella and C. jejuni tend to be found in the large intestine). Generally, stool cultures are performed for all the standard bacteria and Clostridium difficile toxin, a complication of antibiotic therapy to which AIDS patients are particularly vulnerable, since they often receive prolonged courses of antibiotics. If fever is present, blood cultures are part of the work-up, given the high risk of bacteremia. A stool sample for white blood cells can also be useful diagnostically. While lab results are pending after the initial work-up, empiric therapy is often employed if the history and clinical signs suggest a particular etiology. Should the results return negative and empiric therapy fails, an endoscopic tissue biopsy is warranted.

Diagnosis of Shigella or Salmonella is straightforward because the organisms usually can be easily grown from stool samples. Campylobacter is more difficult to grow - stool cultures often return negative, and an endoscopic tissue biopsy sometimes - albeit rarely - necessary for diagnosis (Perlman 1988).

Therapy
Culture and drug sensitivity results generally determine the choice of antibiotic for enteric bacterial infections. Ciprofloxacin may be particularly attractive if organisms are resistant to several antibiotics. Low-dose antibiotic prophylaxis has been recommended if a recurrence is documented following successful initial therapy (Armstrong 1987; Jacobson 1989). Clostridium difficile can usually be treated with metronidazole (Flagyl) or vancomycin.

If the clinician suspects bacteremia in severely ill patients, intravenous (IV) antibiotics should be administered empirically. Documented bacteremia should be treated with IV antibiotics for five to seven days, followed by an additional seven to ten days of oral medication.

Patients with bacteremia caused by Listeria monocytogenes uniformly respond well to antibiotic therapy with ampicillin or penicillin for two to four weeks, with aminoglycosides added for synergy if bacteremia occurs. Vancomycin and TMP/SMX have been successfully used in a small number of patients. In the penicillin-allergic patient, TMP/SMX is the preferred regimen because of its reliable penetration into the cerebrospinal fluid.

PEDIATRIC BACTERIAL INFECTIONS
Recurrent bacterial infections are common early manifestations of HIV infection in children. Serious bacterial infections occur in up to one-third of children with advanced HIV disease (Scott 1984; Bernstein 1985; Krazinski 1988). More than one-fourth of these infections are caused by S. pneumoniae (NICHD IVIG Study Group 1991), although H. influenzae, S. aureus, Pseudomonas and other bacteria are also observed. Bacterial pneumonia occurs in 19 to 63% of HIV-infected children and is associated with bacteremia in 15 to 25% (Johnson 1989). Pneumococcal bacteremia is even more common in HIV-infected children than in adults. Gastrointestinal infections are also common. Infected infants have not been able to develop mature T and B cell responses, and thus recurrent infections present serious, often life-threatening challenges. Unusual manifestations of bacterial infections occur such as non-bacteremic urinary tract infections secondary to diarrhea. P. aeruginosa bacteremia, associated with pulmonary infiltrates, skin lesions, otitis media, lymphadenitis, abdominal abscesses, and meningitis has been reported. Cellulitis, lymphadenitis, and chronic draining otitis media are seen in children before developing OIs. The CDC case definition for pediatric AIDS includes recurrent serious bacterial infections.

Therapy and Prevention
Treatment of bacterial infections in children is similar to treatment in adults, with empiric antibiotic treatment during febrile episodes, modified according to the results of cultures. However, given the high incidence of bacterial infections, increased emphasis has been placed upon prevention of infection or prevention of recurrence in children. Clinical trials of intravenous immunoglobulin (IVIG) have reported conflicting effects on serious bacterial infections in children. Subset analysis suggests that this expensive treatment may only work well in children with CD4 counts over 200. ACTG 051 enrolled 255 symptomatic HIV-infected children in a double-blind, placebo-controlled study comparing AZT alone to monthly infusions of IVIG (400 mg/kg) plus AZT (Spector 199?). After a median follow-up of 30 months, no significant benefit beyond that provided by AZT and PCP prophylaxis with TMP/SMX was observed.

Contrary results were reported by the National Institute of Child Health and Development (NICHD 1991), which enrolled 372 symptomatic HIV-positive children in a double-blind placebo-controlled study of IVIG 400 mg/kg once a month. Equal numbers of patients in each group also received AZT (39% overall) and PCP prophylaxis (48% overall). After a median follow-up of 17 months, an interim analysis showed that among the 317 children who entered the study with CD4 cell counts above 200, 12/162 (7%) IVIG recipients experienced a lab-proven serious bacterial infection, compared with 24/155 (15%) placebo recipients. For children with entry CD4 counts below 200, there was no difference in the rate of these infections. Mortality rates were equal (31 deaths in each group).

Antibiotic prophylaxis is also under consideration. Currently, the ACTG is conducting ACTG 254, a Phase II/III randomized trial of atovaquone and azithromycin compared to TMP/SMX for prevention of bacterial infections in HIV-infected children between two and eight years old.

*

Angulo FJ, Swerdlow DL: Bacterial enteric infections in persons infected with human immunodeficiency virus. Clin Infect Dis, 21 Suppl 1: S84-93, 1995.
Armstrong D: Opportunistic infections in the acquired immune deficiency syndrome. Semin Oncol 14:40-7.872, 1987.
Arzuaga J, Moreno S, Miralles P, et al.: Lower respiratory tract-infections in HIV-infected patients. 10th Intl Conf AIDS, Yokohama, Japan, 1994.
Ballet JJ, Sulcebe G, Couderc LJ, et al.: Impaired anti-pneumococcal antibody response in patients with AIDS-related persistent generalized lymphadenopathy. Clin Exp Immunol 68:479-87, 1987.
Baron AD, et al.: Pseudomonas aeruginosa bronchopulmonary infection in late human immunodeficiency virus disease. Am Rev resp Dis 148;992., 1993.
Bender BS, Frank MM, Lawley TJ, et al.: Defective reticuloendothelial system Fc-receptor function in patients with acquired immunodeficiency syndrome. J Infect Dis 152:409-12, 1985.
Bender BS, Bohnsack JF, Sourlis SH, et al.: Demonstration of defective C3-receptor-mediated clearance by the reticuloendothelial system in patients with acquired immunodeficiency syndrome. J Clin Invest 79:715-20, 1987.
Bernstein LJ, Kreiger BZ, Novick B, et al.: Bacterial infection in the acquired immunodeficiency syndrome of children. Pediatr Dis 4:472-5, 1985.
Blaser MJ, et al.: Recurrent shigellosis complicating human immunodeficiency virus infection: failure of pre-existing antibodies to confer protection. Am J Med. 86(1):105-7, 1989.
Brunkhorst U, Sturner M, Willers H, et al.: Efficacy of intravenous immunoglobulin in patients with advanced HIV-1 infection: a randomized clinical study. Infection 18:86-90, 1990.
Celum CL, Chaisson RE, Rutherford GW: Incidence of salmonellosis in patients with AIDS. J Infect Dis 156;998-1002, 1987.
Centers for Disease Control: Revision of the CDC surveillance case definition for acquired immunodeficiency syndrome. MMWR 36:3S-9S, 1987.
Centers for Disease Control and Prevention (CDC). 1997 USPHS/IDSA Guidelines for the Prevention of Opportunistic Infections in Persons Infected with Human Immunodeficiency Virus. MMWR 46:RR-12:1-55, 1997.
Chaisson RE: Bacterial pneumonia in patients with human immunodeficiency virus infection. Seminars in Respiratory Infections, 4(2):133-8, 1989.
Chaisson RE: Infections due to encapsulated bacteria, Salmonella, Shigella, and Campylobacter. Infect Dis Clin N Am 2(2): 475-84, 1988.
Chaisson RE, Keruly J, Gallant JE, Moore RD: Risk factors for bacterial pneumonia in HIV disease [abstract: 250] 35th Annual Meeting, Infectious Disease Society of America (IDSA), San Francisco, 1997.
Currier JS, Williams P, Feinberg J, et al.: ACTG 815: a prospective study of bacterial infections in advanced HIV disease [abstract]. 4th Conference on Retroviruses and Opportunistic Infections, Washington, D.C., 1997.
Currier JS, Feinberg J: Bacterial infections in HIV disease. AIDS Clin Rev, 1995-1996:131-52, 1996.
de La Rubia F, Clavo A, Lopez Prieto D, et al.: Antimicrobial susceptibility of Streptococcus pneumoniae in HIV patients (abstract: PB0568). 10th Intl Conf AIDS, Yokohama Japan, 1994.
Dieterich DT, Poles MA, Lew EA: Gastrointestinal Manifestations of HIV disease. In Textbooks of AIDS Medicine, Published by Williams & Wilkins. 541-554, 1994.
Dirienzo G, van der Horst C, Frame P, et al.: Prevention of bacterial infection in AIDS: A randomized trial of three agents [abstract:: 200]. 35bh IDSA Meeting, San Francisco, 1997.
Ellis M, Gupta S, Galant S, et al.: Impaired neutrophil function in patients with AIDS or AIDS-related complex: a comprehensive evaluation. J Infect Dis 158:1268-76, 1988.
Fichtenbaum CJ, Woeltje KF, Powderly WG: Serious Pseudomonas aeruginosa infections in patients infected with human immunodeficiency virus: a case-control study. Clin Infect Dis 19:417-422, 1994.
Franzetti F, Cernuschi M, Esposito R: Pseudomonas infections in patients with AIDS and AIDS-related complex. J Intern Med 231:437-43, 1992.
Garcia-Leoni ME, Moreno S, Rodeno P, et al.: Pneumococcal pneumonia in adult hospitalized patients infected with the human immunodeficiency virus. Arch Intern Med 152:1808-12, 1992.
Glaser JB, Volpe S, Aguirre A, et al. Zidovudine improves response to pneumococcal vaccine among persons with AIDS and AIDS-related complex. J Infect Dis 164:761-4, 1991.
Godofsky EW, Zinreich J, Armstrong M, et al.: Sinusitis in HIV-infected patients: a clinical and radiographic review. Am J Med 93:163-70, 1992.
Gould SJ: Full House: The Spread of Excellence from Plato to Darwin. New York: Harmony Books, 1996.
Greenberg AE, Thomas PA, Landesman SH, et al.: The spectrum of HIV-1-related disease among outpatients in New York City. AIDS 6:849-59, 1992.
Hardy WD, Feinberg J, Finkelstein DM, et al.: A controlled trial of trimethoprim-sulfamethoxazole or aerosolized pentamidine for secondary prophylaxis of Pneumocystis carinii pneumonia in patients with the acquired immunodeficiency syndrome. AIDS Clinical Trials Group Protocol 021. N Engl J Med 237:1824-8, 1992.
Holbrook KA, Klein RS, Hartel D, et al.: Staphylococcus aureus nasal colonization in HIV seropositive and seronegative drug users [abstract]. 35th IDSA Meeting, San Francisco, 1997.
Huang KL, Ruben FL, Rinaldo CR Jr, et al.: Antibody responses after influenza and pneumococcal immunization in HIV-infected homosexual men. JAMA 257:2047-50, 1987.
Huebner J; Czerwenka W; Gruner E, et al.: Shigellemia in AIDS patients: case report and review of the literature. Infection. 21(2):122-4, 1993.
Jacobson MA, Hahn SM, Gerberding JL, et al.: Ciprofloxacin for Salmonella bacteremia in the acquired immunodeficiency syndrome (AIDS). Ann Intern Med 110:1027-9, 1989.
Janoff EN, Breiman RF, Daley CL, et al.: Pneumococcal disease during HIV infection: epidemiologic, clinical, and immunologic perspectives. Ann Intern Med 117:314-24, 1992.
Johnson JP, Nair P, Hines SE, et al.: Natural history and serologic diagnosis of infants born to human immunodeficiency syndrome virus-infected women. Am J Dis Child 143:1147-53, 1989.
Jurado RL, Farley MM, Pereira E, et al.: Increased risk of meningitis and bacteremia due to Listeria monocytogenes in patients with human immunodeficiency virus infection. Clin Infect Dis 17:224-7, 1993.
Kaykova Y, Reinaud G, O'Leary J, Bandres JC: Analysis of neutrophil function in HIV infected individuals with high and low CD4 counts [abstract]. 35th IDSA Meeting, San Francisco, 1997.
Keiser P, Higgs E, Peterson D: Neutropenia is associated with bacterial infections [abstract: PB0574]. In: 10th Intl Conf AIDS, Yokohama, Japan, 1994.
Kielhofner M, Atmar RL, Hamill RJ: Life-threatening Pseudomonas aeruginosa infections in patients with human immunodeficiency virus infection. Clin Infect Dis 14:403-11, 1992.
Klein RS, Selwyn PA, Maude D, et al.: Response to pneumococcal vaccine among asymptomatic heterosexual partners of persons with AIDS and intravenous drug users infected with human immunodeficiency virus. J Infect Dis 160:826-31, 1989.
Klontz KC, Lieb S, Schreiber M, et al.: Syndromes of Vibrio vulnificus infections: clinical and epidemiologic features in Florida cases. 1981-1987. Ann Intern Med 109:318-23, 1988.
Kotler DP, Orenstein JM: Diarrhea and malabsorption due to enterocyte-adherent bacterial infection in a patient with AIDS. Ann Intern Med 116:127-8, 1993.
Kotler DP, Giang TT, Thiim M, et al.: Chronic bacterial enteropathy in patients with AIDS. J Infect Dis 171:552-8, 1995.
Krazinski K, Borkowsky W, Bonk S, et al. Bacterial infections in human immunodeficiency virus-infected children. Pediatr Infect Dis 7:323-8, 1988.
Lane HC, Masur H, Edgar LC, et al.: Abnormalities of B-cell activation and immunoregulation in patients with the acquired immunodeficiency syndrome. N Engl J Med 309:453-8, 1983.
Mars ME, Quinson AM, North MO, et al.: Contribution of intravenous immunoglobulins (IVIG) therapy in HIV infected adults [abstract]. 10th Intl Conf AIDS, Yokohama, Japan, 1994.
Magnenat J, Nicod LP, Auckenthaler R, et al.: Mode of presentation and diagnosis of bacterial pneumonia in human immunodeficiency virus-infected patients. Am Rev Respir Dis 144:917-22, 1991.
Martos A, Podzamczer D, Concejo C: Nocardial infection in HIV-infected patients [abstract]. 9th International Conference on AIDS, Berlin, 1993.
McGrath MS: Immunology of AIDS: overview. In: Cohen PT, Sande MA, Volberding PA, eds. The AIDS knowledge base. Boston: Little, Brown, 1994.
Meiteles LZ, Lucente FE: Sinus and nasal manifestations of the acquired immunodeficiency syndrome. Ear Nose Throat J 69:454-9, 1990.
Mientjes GH, van Ameijden EJ, van den Hoek AJ et al.: Increasing morbidity without rise in non-AIDS mortality among HIV-infected intravenous drug users in Amsterdam. AIDS 6:207-12, 1992.
Molina JM, et al.: Campylobacter infections in HIV-infected patients: clinical and bacteriological features. AIDS 9:881-885, 1995.
Muller F, Froland SS, Brandtzaeg P: Altered IgG-subclass distribution in lymph node cells and serum of adults infected with human immunodeficiency virus (HIV). Clin Exp Immunol 78:153-158, 1989.
Murray JF, Felton CP, Garay SM, et al. Pulmonary complications of the acquired immunodeficiency syndrome: report of a National Heart, Lung, and Blood Institute workshop. N Engl J Med 310:1682-8, 1984.
National Institute of Child Health and Human Development Intravenous Immunoglobulin Study Group. Intravenous immune globulin for the prevention of bacterial infection in children with symptomatic human immunodeficiency virus infection. N Engl J Med 325:73-80, 1991.
Nelson MR, Shanson DC, Hawkins D.: Shigella in HIV infection [letter]. AIDS 5(8):1031-2, 1991.
Nelson MR, Shanson DC, Barter GJ: Pseudomonas septicemia associated with HIV. AIDS 5:761-3, 1991.
Nelson MR, Shanson DC, Hawkins DA: Salmonella, Campylobacter, and Shigella in HIV-seropositive patients. AIDS 6:1495-8, 1992.
Omenaca C, Astiz M, Yarrish R, et al.: A prospective study of bacteremia in patients with HIV infection [abstract]. 35th IDSA Meeting, San Francisco, 1997.
Perlman DM, Ampel NM, Schifman RB, et al.: Persistent Campylobacter jejuni infections in patients infected with human immunodeficiency virus (HIV). Ann Intern Med 108:540-6.88161893, 1988.
Pesola GR, Charles A: Pneumococcal bacteremia with pneumonia: mortality in acquired immunodeficiency syndrome. Chest 101:150-5, 1992.
Polsky B, Gold JW, Whimbey E, et al.: Bacterial pneumonia in patients with the acquired immunodeficiency syndrome. Ann Intern Med 104:38-41, 1986.
Redd SC, Rutherford GW III, Sande MA, et al.: The role of human immunodeficiency virus infection in pneumococcal bacteremia in San Francisco residents. J Infect Dis 162:1012-7, 1990.
Reimer CB, Black CM, Holman RC, et al.: Hypergammaglobulinemia associated with human immunodeficiency virus infection. Monogr Allergy 23:83-96, 1988.
Revision of the CDC surveillance case definition for acquired immunodeficiency syndrome. MMWR 36:1S-15S, 1987.
Rosenberg A, Atiyeh L, Seneff M, et al.: The microbiology of patients with AIDS admitted to the intensive care unit: the importance of bacterial infections [abstract]. 4th Conference on Retroviruses and Opportunistic Infection, Washington, D.C., 1997.
Ruizi JD, Rosen MJ: The changing spectrum of pulmonary complications of HIV-infection (abstract). Am Rev Respir Dis 145:A820, 1992.
Schrager LK, et al.: Bacterial infections in AIDS patients. AIDS, 2(Supp.1): S183-9, 1990.
Scott GB, Buck BE, Leterman JG, et al.: Acquired immunodeficiency syndrome in infants. N Engl J Med 310:76-81, 1984.
Selwyn PA, et al.: Clinical manifestations and predictors of disease progression in drug users with human immunodeficiency virus infection. N Engl J Med 327:1697-703, 1992.
Small CB, et al.: Sinusitis and atopy in human immunodeficiency virus infection. J Infect Dis 167:283-90, 1993.
Smith PD, Lane HC, Gill VJ, et al.: Intestinal infection in persons with the acquired immunodeficiency syndrome (AIDS) Ann Intern Med 108:328-33, 1988.
Sooy CD: Impact of AIDS on otolaryngology head and neck surgery. In: Meyers EN, ed. Advances in otolaryngology - head and neck surgery. Vol.1. Chicago: Year Book 1987;1-27.
Sorvillo FJ, Lieb LE, Waterman SH, et al.: Incidence of campylobacteriosis among patients with AIDS in Los Angeles County. J Acquir Immune Defic Syndr 1991;4:598-602.
Spector SA, Gelber RD, Mc Grath N, et al.: A controlled trial of intravenous immune globulin for the prevention of serious bacterial infections in children receiving zidovudine for advanced human immunodeficiency virus infection. N Engl J Med 331: 1181-7, 1994.
Sperber SJ, et al.: Salmonellosis during HIV infection with human immunodeficiency virus. Rev Infect Dis 9:925-34, 1987.
Steinhart R, Reingold AL, Taylor F, et al.: Invasive Haemophilus influenzae infections in men with HIV infection. JAMA 268:3350-2, 1992.
Steinhoff MC, et al.: Antibody responses to Haemophilus influenzae type B vaccines in men with HIV infection. N ENGL J MED 325: 1837-42, 1991.
Sullivan JF, Benson CA, Sha BE, et al.: Bordetella bronchiseptica infections in patients; with AIDS [abstract: 273]. 32nd IDSA, Orlando, 1994.
Tami TA, Wawrose S: Diseases of the nose and paranasal sinus in the acquired immunodeficiency virus-infected population. Otolaryngol Clin North Am 25:1199-210, 1992.
Terpstra FG, Ai BJ, Roos MT, et al.: Longitudinal study of leukocyte functions in homosexual men seroconverted for HIV: rapid and persistent loss of B cell function after HIV infection. Eur J Immunol 19:667-73, 1989.
Thompson C, et al.: Etiology of acute sinusitis in HIV-infection [abstract: WS-B08-6] 9th Intl Conf AIDS, Berlin, 1993.
Tocalli L, Nardi G, Mammino A, et al.: Salmonellosis diagnosed by the laboratory of the 'L Sacco' Hospital of Milan in patients with HIV disease. Eur J Epidemiol 7:690-5, 1991.
Uttamchandani RB, Daikos GL, Reyes RR, et al.: Nocardiosis in 30 patients with advanced human immunodeficiency virus infection: clinical features and outcome. Clin Infect Dis 18:348-53, 1994.
Verville TD, Huycke MM, Greenfield RA, et al.: Rhodococcus equi infections of humans. 12 cases and a review of the literature. Medicine 73:119-32, 1994.
von Schoennberg MA, Grant AD, Grant, HR et al.: Paranasal sinus disease in HIV antibody positive patients [abstract: PO-B06-1106] 9th Intl Conf AIDS, Berlin, 1993.
Whitman CM, Griffin PM: Commentary: preventing Vibrio vulnificus infection in the high-risk patient. Infectious Disease in Clinical Practice, 2:275-6, 1993.
Witt DJ, Craven DE, McCabe WR, et la.: Bacterial infections in adult patients with the acquired immune deficiency syndrome (AIDS) and AIDS-related complex. Am J Med 82:900-6, 1987.
Wawrose SF, Tami TA, Amoils CP, et al.: The role of guaifenesin in the treatment of sinonasal disease in patients infected with the human immunodeficiency virus (HIV). Laryngoscope 102: 1225-8, 1992.
Zurlo JJ, Feuerstein IM, Lebovics R, et al.: Sinusitis in HIV-1 infection. Am J Med 93:157-62, 1992.

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